Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors

被引：0

作者：

Jinushi, Koichi ^{[1
,2
]}

Saito, Takuro ^{[1
,2
]}

Kurose, Koji ^{[3
]}

Suzuki, Susumu ^{[4
,5
]}

Kojima, Takashi ^{[6
]}

Takahara, Taishi ^{[7
]}

Makino, Tomoki ^{[1
]}

Ogawa, Tetsuya ^{[8
]}

Nishikawa, Hiroyoshi ^{[9
,10
,11
]}

Kakimi, Kazuhiro ^{[12
,13
]}

Iida, Shinsuke ^{[14
,15
]}

Nakajima, Jun ^{[16
]}

Doki, Yuichiro ^{[1
]}

Oka, Mikio ^{[17
]}

Ueda, Ryuzo ^{[10
]}

Wada, Hisashi ^{[18
]}

机构：

[1] Osaka Univ, Dept Gastroenterol Surg, Grad Sch Med, Sch Med, Suita, Osaka Prefectur, Japan

[2] Osaka Univ, Dept Clin Res Tumor Immunol, Sch Med, Grad Sch Med, Suita, Osaka Prefectur, Japan

[3] Kawasaki Med Sch, Dept Resp Med, Kurashiki, Japan

[4] Aichi Med Univ, Res Creat Support Ctr, Nagakute, Aichi, Japan

[5] Aichi Med Univ, Tumor Immunol, Nagakute, Aichi, Japan

[6] Natl Canc Ctr Hosp East, Dept Gastroenterol & Gastrointestinal Oncol, Kashiwa, Chiba, Japan

[7] Aichi Med Univ Hosp, Dept Surg Pathol, Nagakute, Aichi Prefectur, Japan

[8] Aichi Med Univ, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Nagakute, Japan

[9] Natl Canc Ctr Japan, Div Canc Immunol, Chuo, Tokyo, Japan

[10] Nagoya Univ, Dept Immunol, Grad Sch Med, Fac Med, Nagoya, Aichi Prefectur, Japan

[11] Kyoto Univ, Ctr Canc Immunotherapy & Immunobiol, Div Canc Immune Multicellular Syst Regulat, Grad Sch Med, Kyoto, Japan

[12] Kindai Univ, Dept Immunol, Fac Med, Grad Sch Med Sci, Sayama, Osaka, Japan

[13] Univ Tokyo Hosp, Dept Immunotherapeut, Bunkyo Ku, Tokyo, Japan

[14] Nagoya City Univ, Dept Hematol & Oncol, Grad Sch Med Sci, Nagoya, Aichi, Japan

[15] Nagoya City Univ, Med Sch, Nagoya, Aichi Prefectur, Japan

[16] Univ Tokyo, Dept Thorac Surg, Bunkyo Ku, Tokyo, Japan

[17] Kawasaki Med Sch, Dept Immuno Oncol, Kurashiki, Japan

[18] Nagoya Univ, Dept Immunol, Grad Sch Med, Nagoya, Japan

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2025年 / 13卷 / 04期

关键词：

Immunotherapy; Solid tumor; T regulatory cell - Treg; Antibody; HUMANIZED ANTI-CCR4 ANTIBODY; CELL LEUKEMIA-LYMPHOMA; ADVERSE EVENTS; KW-0761; CANCER; SAFETY;

D O I：

10.1136/jitc-2024-010634

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Effector regulatory T cells expressing C-C chemokine receptor 4 (CCR4) suppress antitumor immune responses. We conducted a phase I clinical trial to evaluate the safety and efficacy of preoperative combination therapy with mogamulizumab (an anti-CCR4 antibody) and nivolumab (an anti-programmed death-1 antibody) in patients with solid tumors.Methods Patients with operable solid tumors were enrolled in a 3+3 design, with preoperative nivolumab (3.0 mg/kg) administered intravenously every 2 weeks three times and mogamulizumab at 0.1 mg/kg (cohort 1), 0.3 mg/kg (cohort 2), or 1.0 mg/kg (cohort 3) every week four times. The primary endpoints were safety and the effects of depleting Forkhead box P3+ (FoxP3+) T cells in the tumor.Results 16 patients were enrolled between June 2016 and April 2020, including those with renal (n=7), lung (n=5), esophageal (n=3), and oral (n=1) cancers. Grade 3-4 treatment-related adverse events were observed in 6 of 16 patients, with lymphopenia (25%) and maculopapular rash (13%) being the most frequent. Grade 5 interstitial pneumonia was observed in one patient; however, the cause of death was disease progression. There were three partial responses (PRs) (one lung and two esophageal cancers) among clinical responses and one complete response (one lung cancer) and nine PRs (five kidney, two lung, and two esophageal cancers) among pathological responses. CCR4+FoxP3+ T cells were depleted in the tumors of all patients and increases in lymphocytes in tumor tissue according to the tumor immune microenvironment classification were observed in 50% of the patients, which correlated with a better prognosis.Conclusions The preoperative combination of mogamulizumab and nivolumab was safely managed, exerted antitumor effects, and may be an effective option in the preoperative setting.Trial registration number The present study was registered with ClinicalTrials.gov as NCT02946671 (registration date 2016-10-05).

引用

页数：12

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